Kidney Week

Abstract: SA-PO276

Glomerular Injury Related to Immune Related Adverse Events: IgA Nephropathy After Nivolumab Therapy for Postoperative Recurrence of Lung Cancer

Session Information

• Trainee Case Reports - VI
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Iwaki, Maho, Department of Nephrology, Tokushima University, Tokushima, Japan

Maho Iwaki,

• Kishi, Seiji, Department of Nephrology, Tokushima University, Tokushima, Japan

Seiji Kishi,

• Minato, Masanori, Department of Nephrology, Tokushima University, Tokushima, Japan

Masanori Minato,

• Tamaki, Masanori, Department of Nephrology, Tokushima University, Tokushima, Japan

Masanori Tamaki,

• Kishi, Fumi, Department of Nephrology, Tokushima University, Tokushima, Japan

Fumi Kishi,

• Murakami, Taichi, Department of Nephrology, Tokushima University, Tokushima, Japan

Taichi Murakami,

• Abe, Hideharu, Department of Nephrology, Tokushima University, Tokushima, Japan

Hideharu Abe,

• Nagai, Kojiro, Department of Nephrology, Tokushima University, Tokushima, Japan

Kojiro Nagai,

Introduction

Immune checkpoint inhibitors (ICIs; anti-PD-1 or anti-CTLA-4) are becoming a common and an important therapeutic option for cancer patients. ICIs are associated with a unique category of side effects calld immune-related adverse events (irAE) and physicians should be aware of its clinical importance. According to previous reports, renal irAEs are less frequent than other organ involvement and glomerulonephritis is not typical. In this report, we present a case of nivolumab associated mesangial proliferative glomerulonephritis (IgA nephropathy), previously not reported.

Case Description

A 72-year-old man with postoperative recurrence of lung squamous cell carcinoma treated with nivolumab (anti-PD-1 antibody) who developed proteinuria and worsening kidney function was referred to our department.Ten months previously, he had been started on intravenous nivolumab therapy because of the postoperative recurrence of lung squamous cell carcinoma (cT3N2M0 stage IIIA). Six months after the first nivolumab treatment, the patient’s creatinine began to increase and proteinuria was noted.Kidney biopsy showed mesangial proliferative glomerulonephritis with C3 and IgA deposition.Electron-microscopy demonstrated a small amount of high electron-dense deposits in the subepithelial and mesangial regions.After drug withdrawal, the proteinuria improved and the deterioration of the renal function was halted.

Discussion

To our knowledge, this is the very rare case of biopsy-proven immune complex glomerulonephritis following treatment with ICI. Although it may be difficult to prove a causal relationship of ICI and IgA nephropathy, we suspect nivolumab played a role in the pathogenetis of IgA nephropathy. The patient did not have disease-precipitating events such as upper respiratoty infection prior to the disease onset and we observed the decrease in proteinuria and improvement in serum creatinine after drug withdrawal. The previous study showed PD-1 knockout mice develop immune complex glomerulonephritis. These findings suggested that PD-1 signaling pathway is important to minimize T-cell-mediated renal inflammation. Glomerular lesions have been exacerbated from subacute to chronic course in our case, which suggests the possibility of another type of disease progression.